ArticleThe American journal of pathology2016
TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-κB Pathway.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
105 citing papers in PubMed, 2 syntheses or guidelines pooled it, 199 citations in OpenAlex.
- The role of natural products in the intestinal barrier: a bibliometric analysis from 2004 to 2025.Frontiers in immunology · 2026Pooled it
- Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis.Frontiers in genetics · 2023Pooled it
- Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding.Frontiers in immunology · 2022Trial
- The effect of probiotic supplementation on performance, inflammatory markers and gastro-intestinal symptoms in elite road cyclists.Journal of the International Society of Sports Nutrition · 2021Trial
- Article
- Harmaline and the gut-brain-immune axis: a novel therapeutic avenue in neuroinflammation and ulcerative colitis.Inflammopharmacology · 2026Review
- Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon.Molecules (Basel, Switzerland) · 2026Review
- Bidirectional interplay between gut and liver in inflammatory bowel disease and hepatobiliary conditions.Clinical and experimental medicine · 2026Review
- Crosstalk between inflammation and autophagy in CeD organoids.Scientific reports · 2026Article
- Gut microbiota shifts in spaceflight: a case study evidence and countermeasures for microbial homeostasis.3 Biotech · 2026Review
- Cellular Stress, Inflammation and Barrier Damage in Gut Epithelial Cells Caused by Aspartame.Allergy · 2026Article
- Probiotic bacteria Bifidobacterium bifidum upregulation of intestinal epithelial tight junction barrier is mediated by TLR-2/TLR-6 receptor complex activation of occludin gene.NPJ biofilms and microbiomes · 2026Article
- Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.Frontiers in immunology · 2026Review
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- Ferroptosis-immune crosstalk in ionizing radiation-induced testicular injury: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Fermented cotton stalks preserve colonic epithelial integrity in Hu sheep via the microbiota-metabolite-NF-κB/MLCK axis and mitigate the adverse effects of direct feeding.Frontiers in nutrition · 2026Article
- Dietary L-arginine supplementation exerts preventive effects on colitis through modulation of the gut microbiota.Frontiers in nutrition · 2026Article
- Article
- Dietary Flavonoids as Cross-System Modulators of Hypertension and Intestinal Permeability.Molecules (Basel, Switzerland) · 2025Review
- The circRNA-mediated ceRNA molecular regulatory network in fatigue-type type 2 diabete.Journal of translational medicine · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor (TNF)-α, a key mediator of intestinal inflammation, causes an increase in intestinal epithelial tight junction (TJ) permeability by activating myosin light chain kinase (MLCK; official name MYLK3) gene. However, the precise signaling cascades that mediate the TNF-α-induced activation of MLCK gene and increase in TJ permeability remain unclear. Our aims were to delineate the upstream signaling mechanisms that regulate the TNF-α modulation of intestinal TJ barrier function with the use of in vitro and in vivo intestinal epithelial model systems. TNF-α caused a rapid activation of both canonical and noncanonical NF-κB pathway. NF-κB-inducing kinase (NIK) and mitogen-activated protein kinase kinase-1 (MEKK-1) were activated in response to TNF-α. NIK mediated the TNF-α activation of inhibitory κB kinase (IKK)-α, and MEKK1 mediated the activation of IKK complex, including IKK-β. NIK/IKK-α axis regulated the activation of both NF-κB p50/p65 and RelB/p52 pathways. Surprisingly, the siRNA induced knockdown of NIK, but not MEKK-1, prevented the TNF-α activation of both NF-κB p50/p65 and RelB/p52 and the increase in intestinal TJ permeability. Moreover, NIK/IKK-α/NF-κB p50/p65 axis mediated the TNF-α-induced MLCK gene activation and the subsequent MLCK increase in intestinal TJ permeability. In conclusion, our data show that NIK/IKK-α/regulates the activation of NF-κB p50/p65 and plays an integral role in the TNF-α-induced activation of MLCK gene and increase in intestinal TJ permeability.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.